Roger Abounader

Education

  • PhD, University of Heidelberg, Germany
  • MD, University of Heidelberg, Germany
  • BS, American University of Beirut, Lebanon

Primary Appointment

  • Professor, Microbiology, Immunology, and Cancer Biology

Contact

Research Interest(s)

Basic and translational brain tumor research

Research Description

Our research focuses on understanding the molecular basis of brain tumor and glioblastoma development and growth and on using the acquired knowledge to identify new therapeutic targets and develop new therapeutic approaches. Specifically, the following projects are ongoing in the lab at this time:

1. MicroRNAs in brain tumors:

We are studying the expressions, mechanisms of action and functions of several microRNAs that are predicted to target or mediate the effects of important oncogenic molecules in brain tumors. We are also using novel global microRNA target screening approaches (PAR-CLIP and CLASH) to uncover the compendium of microRNA targets in brain tumors. The ultimate goal is to understand the role of microRNAs in brain tumor development and growth and to identify master regulatory microRNAs that can be used or targeted for therapy with novel molecular delivery approaches.

2. MET and other receptor tyrosine kinases (RTK) in brain tumors:

We previously established the MET pathway as a contributor to brain tumor malignancy. Clinically applicable inhibitors of MET have been subsequently developed but have thus far failed to achieve significant effects in human patients. We hypothesized that this failure is due to signaling redundancy and compensatory mechanisms involving various other pathways and molecules including other RTKs. Our goal is to understand how MET interacts with these pathways and molecules, and to use this understanding to develop new therapies that target MET in combination with other molecules. We are also interested in uncovering the determinants of sensitivity and resistance to MET inhibitors in order to better select patients that will benefit for MET inhibition and to develop new approaches for overcoming resistance to anti-MET drugs.

3. Novel interactions between the tumor suppressor PTEN and mutant p53:

Novel interactions between the tumor suppressor PTEN and mutant p53: We discovered that the tumor suppressor PTEN can exhibit unexpected tumor-promoting properties. We have evidence that these tumor-promoting properties of PTEN are due to its interactions with gain-of-function mutant p53. We are systematically studying these, previously unknown, interactions between PTEN and mutant-p53 and their implications for prognosis and the design of anti-tumor therapies. The findings will provide new mechanistic insights into the interactions between PTEN and p53 mutants in human cancer, have prognostic value and determine the settings and pre-conditions under which manipulating tumor suppressor expression and function can lead to successful anti-tumor therapies.

4. T type calcium channels in glioblastoma stem cells:

We recently developed interest in studying the molecular mechanisms and targeting for glioblastoma therapy of T type calcium channels. The goal is to understand their role in cancer stem cells and to develop channel blockers as novel adjuvants for the clinical therapy of glioblastoma.

Selected Publications

  • Cruickshanks N, Zhang Y, Yuan F, Pahuski M, Gibert M, Abounader R. Role and Therapeutic Targeting of the HGF/MET Pathway in Glioblastoma. Cancers. 2017;9(7). PMID: 28696366 | PMCID: PMC5532623
  • Olmez I, Brenneman B, Xiao A, Serbulea V, Benamar M, Zhang Y, Manigat L, Abbas T, Lee J, Nakano I, Godlewski J, Bronisz A, Abounader R, Leitinger N, Purow B. Combined CDK4/6 and mTOR Inhibition Is Synergistic against Glioblastoma via Multiple Mechanisms. Clinical cancer research : an official journal of the American Association for Cancer Research. 2017;23(22): 6958-6968. PMID: 28814434 | PMCID: PMC5690820
  • Olmez I, Love S, Xiao A, Manigat L, Randolph P, McKenna B, Neal B, Boroda S, Li M, Brenneman B, Abounader R, Floyd D, Lee J, Nakano I, Godlewski J, Bronisz A, Sulman E, Mayo M, Gioeli D, Weber M, Harris T, Purow B. Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha. Neuro-oncology. 2017. PMID: 29048560 | PMCID: PMC5777487
  • Zhang Y, Cruickshanks N, Yuan F, Wang B, Pahuski M, Wulfkuhle J, Gallagher I, Koeppel A, Hatef S, Papanicolas C, Lee J, Bar E, Schiff D, Turner S, Petricoin E, Gray L, Abounader R. Targetable T-type Calcium Channels Drive Glioblastoma. Cancer research. 2017;77(13): 3479-3490. PMID: 28512247 | PMCID: PMC5505315
  • Reon B, Anaya J, Zhang Y, Mandell J, Purow B, Abounader R, Dutta A. Expression of lncRNAs in Low-Grade Gliomas and Glioblastoma Multiforme: An In Silico Analysis. PLoS medicine. 2016;13(12): e1002192. PMID: 27923049 | PMCID: PMC5140055
  • Vega R, Zhang Y, Curley C, Price R, Abounader R. 370 Magnetic Resonance-Guided Focused Ultrasound Delivery of Polymeric Brain-Penetrating Nanoparticle MicroRNA Conjugates in Glioblastoma. Neurosurgery. 2016;63 210. PMID: 27399567
  • Lee D, Zhang Y, Kassam A, Park M, Gardner P, Prevedello D, Henry S, Horbinski C, Beumer J, Tawbi H, Williams B, Shaffrey M, Egorin M, Abounader R, Park D. Combined PDGFR and HDAC Inhibition Overcomes PTEN Disruption in Chordoma. PloS one. 2015;10(8): e0134426. PMID: 26247786 | PMCID: PMC4527706
  • Awad A, Burns T, Zhang Y, Abounader R. Targeting MET for glioma therapy. Neurosurgical focus. 2014;37(6): E10. PMID: 25434379
  • Feng C, Zhang Y, Yin J, Li J, Abounader R, Zuo Z. Regulatory factor X1 is a new tumor suppressive transcription factor that acts via direct downregulation of CD44 in glioblastoma. Neuro-oncology. 2014;16(8): 1078-85. PMID: 24526308 | PMCID: PMC4096175
  • Floyd D, Zhang Y, Dey B, Kefas B, Breit H, Marks K, Dutta A, Herold-Mende C, Synowitz M, Glass R, Abounader R, Purow B. Novel anti-apoptotic microRNAs 582-5p and 363 promote human glioblastoma stem cell survival via direct inhibition of caspase 3, caspase 9, and Bim. PloS one. 2014;9(5): e96239. PMID: 24805821 | PMCID: PMC4013090
  • Kim J, Zhang Y, Skalski M, Hayes J, Kefas B, Schiff D, Purow B, Parsons S, Lawler S, Abounader R. microRNA-148a is a prognostic oncomiR that targets MIG6 and BIM to regulate EGFR and apoptosis in glioblastoma. Cancer research. 2014. PMID: 24425048 | PMCID: PMC3947487
  • Negishi M, Wongpalee S, Sarkar S, Park J, Lee K, Shibata Y, Reon B, Abounader R, Suzuki Y, Sugano S, Dutta A. A New lncRNA, APTR, Associates with and Represses the CDKN1A/p21 Promoter by Recruiting Polycomb Proteins. PloS one. 2014;9(4): e95216. PMID: 24748121 | PMCID: PMC3991591
  • Zhang Y, Kim J, Mueller A, Dey B, Yang Y, Lee D, Hachmann J, Finderle S, Park D, Christensen J, Schiff D, Purow B, Dutta A, Abounader R. Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma. Cell death and differentiation. 2014;21(5): 720-34. PMID: 24440911 | PMCID: PMC3978301
  • Zhang Y, Schiff D, Park D, Abounader R. MicroRNA-608 and microRNA-34a regulate chordoma malignancy by targeting EGFR, Bcl-xL and MET. PloS one. 2014;9(3): e91546. PMID: 24621885 | PMCID: PMC3951453
  • Dominguez C, Floyd D, Xiao A, Mullins G, Kefas B, Xin W, Yacur M, Abounader R, Lee J, Wilson G, Harris T, Purow B. Diacylglycerol kinase α is a critical signaling node and novel therapeutic target in glioblastoma and other cancers. Cancer discovery. 2013;3(7): 782-97. PMID: 23558954 | PMCID: PMC3710531
  • Guessous F, Alvarado-Velez M, Marcinkiewicz L, Zhang Y, Kim J, Heister S, Kefas B, Godlewski J, Schiff D, Purow B, Abounader R. Oncogenic effects of miR-10b in glioblastoma stem cells. Journal of neuro-oncology. 2013;112(2): 153-63. PMID: 23307328 | PMCID: PMC3609924
  • Huang X, Zhang Y, Tang Y, Butler N, Kim J, Guessous F, Schiff D, Mandell J, Abounader R. A novel PTEN/mutant p53/c-Myc/Bcl-XL axis mediates context-dependent oncogenic effects of PTEN with implications for cancer prognosis and therapy. Neoplasia (New York, N.Y.). 2013;15(8): 952-65. PMID: 23908595 | PMCID: PMC3730046
  • Kefas B, Floyd D, Comeau L, Frisbee A, Dominguez C, Dipierro C, Guessous F, Abounader R, Purow B. A miR-297/hypoxia/DGK-α axis regulating glioblastoma survival. Neuro-oncology. 2013;15(12): 1652-63. PMID: 24158111 | PMCID: PMC3829588
  • Kofman A, Kim J, Park S, Dupart E, Letson C, Bao Y, Ding K, Chen Q, Schiff D, Larner J, Abounader R. microRNA-34a promotes DNA damage and mitotic catastrophe. Cell cycle (Georgetown, Tex.). 2013;12(22): 3500-11. PMID: 24091633 | PMCID: PMC3906336
  • Kofman A, Letson C, Dupart E, Bao Y, Newcomb W, Schiff D, Brown J, Abounader R. The p53-microRNA-34a axis regulates cellular entry receptors for tumor-associated human herpes viruses. Medical hypotheses. 2013;81(1): 62-7. PMID: 23643704 | PMCID: PMC3676726
  • Catania A, Maira F, Skarmoutsou E, D'Amico F, Abounader R, Mazzarino M. Insight into the role of microRNAs in brain tumors (review). International journal of oncology. 2011;40(3): 605-24. PMID: 22179098
  • Guessous F, Yang Y, Johnson E, Marcinkiewicz L, Smith M, Zhang Y, Kofman A, Schiff D, Christensen J, Abounader R. Cooperation between c-Met and focal adhesion kinase family members in medulloblastoma and implications for therapy. Molecular cancer therapeutics. 2011;11(2): 288-97. PMID: 22188814 | PMCID: PMC3277676
  • Kofman A, Abounader R. When tumor cells make blood vessels: implications for glioblastoma therapy. Future oncology (London, England). 2011;7(7): 841-3. PMID: 21732755 | PMCID: PMC3278210
  • Kofman A, Marcinkiewicz L, Dupart E, Lyshchev A, Martynov B, Ryndin A, Kotelevskaya E, Brown J, Schiff D, Abounader R. The roles of viruses in brain tumor initiation and oncomodulation. Journal of neuro-oncology. 2011;105(3): 451-66. PMID: 21720806 | PMCID: PMC3278219
  • Zhang Y, Dutta A, Abounader R. The role of microRNAs in glioma initiation and progression. Frontiers in bioscience : a journal and virtual library. 2011;17 700-12. PMID: 22201769 | PMCID: PMC3278211
  • Guessous F, Zhang Y, Kofman A, Catania A, Li Y, Schiff D, Purow B, Abounader R. microRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell cycle (Georgetown, Tex.). 2010;9(6): 1031-6. PMID: 20190569 | PMCID: PMC3278213
  • Zhang Y, Guessous F, Kofman A, Schiff D, Abounader R. XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and NSCLC. IDrugs : the investigational drugs journal. 2010;13(2): 112-21. PMID: 20127563 | PMCID: PMC3268517
  • Guessous F, Zhang Y, diPierro C, Marcinkiewicz L, Sarkaria J, Schiff D, Buchanan S, Abounader R. An orally bioavailable c-Met kinase inhibitor potently inhibits brain tumor malignancy and growth. Anti-cancer agents in medicinal chemistry. 2009;10(1): 28-35. PMID: 20015006 | PMCID: PMC3278215